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=Introduction=

FtsA is a peripheral membrane cell division protein which can bind ATP. It belongs to the actin family of proteins that includes actin, hsp 70, and sugar kinase. FtsA is an ATPase and is homologous to the ATPase domain of actin family of proteins. FtsZ is another important cell division protein, and is a structural homologue of eukaryotic tubulin. Polymerization of FtsZ is a crucial step in forming septal ring. The bacterial cell cycle includes events such as initiation of chromosome replication, nucleoid segregation, and cell division. During the cell division, nine proteins will be localized in the cell center and will direct the assembly of the division septum A collection of cell division proteins encoded by FtsA, FtsI, FtsK, FtsL, FtsN, FtsQ, FtsW, FtsZ and zipA are essential for bacterial cell division and function directly in the septation. Assembly of ring proteins happens in a specific order starting with polymerization of the protein FtsZ into the Z ring, with the preceding protein dictating the recruitment of the next one. Localization of FtsA depends on the localization of FtsZ. FtsA will localize to the division site and bind to the FtsZ ring in order to connect the FtsZ molecules and membrane-anchored proteins or integral membrane protein of the septum. Then the rest of the proteins can assemble into the septal ring, which contracts as the septum grows. A specific ratio of FtsA to FtsZ protein is required in cell division. Overproductionof FtsZ can inhibit cell division and Z ring formation, thus preventing the localization of the FtsA.

Structure
The 3D structure of FtsA is similar to structure of the actin family of proteins. Not only are FtsA and actin resembles each other in structure, but they are also similar in their function since both of them are involved bacterial cytokinesis. FtsA contains two domains and each domain separates into two homologous subdomains, 1A and 2A. Both subdomains are composed of five-stranded β sheet surrounded by three helices. The other two smaller subdomains, 1C and 2B, vary amoung actin family and are different in structures. The nucleotide-binding site of FtsA is located in the interdomain cleft formedd by subdomains 1A, 2A and 2B(5). The adenosine is located in a hydrophobic pocket which is made of residues from subdomain 2A and 2B. The phosphate moiety of the nucleotide binds to two loops that connect the first and second strand of subdomain 1A and 2A.

Function
FtsA is present in low amounts, and yet it is essential for cell division. It has been shown that Bacilus subtilis cannot divides efficiently nor sporulate without sufficient amount of FtsA present. The FtsA-specific domain in 1C has an important functional role because its fold and topology is uncommon for the actin family of proteins and is not homologous to any known structure within the actin family. It consists of three-stranded antiparallel β-sheet which lies close to an α helix. In Actin and Hsc70, the subdomain follows the third β strand while in FtsA a helix and the fourth β strand of subdomain 1A are inserted after the β strand. Hexokinase has two short, antiparellel-strand positioned at the same place as subdomain 1C instead of having insertions after the third β strand. It is suggested that the flexibility of subdomain 1C might be related to the nucleotide binding state of the protein since the binding of the nucleotide could stabilize 1C in a specific position. FtsA diretcly interact with C-terminus of FtsZ and it is possible that C-terminus of FtsZ binds to the cleft which is formed by subdomain 1A and 1C and adjusted by the movement of the 1C subdomain. The binding of FtsZ may in turn change the conformation of FtsA that is associated wit ATP conversion. Only phosphorylated form of FtsA can bind ATP, and phosphorylation and ATP binding might inhibit FtsA from interacting with the maturing septum prematurely. Gly336 is conserved in the protein family and is essential in forming the loop structure of the adenosine binding domain. It is predicted that a change in the Gly336 residue could affect the ATP binding activity. Mutation constructed by substituting Asp for Gly336 shows that substitution of Gly336 renders the binding site functionless. =References=